Ask about this productRelated genes to: DNCH1 antibody
- Gene:
- DYNC1H1 NIH gene
- Name:
- dynein cytoplasmic 1 heavy chain 1
- Previous symbol:
- DNECL, DNCL, DNCH1
- Synonyms:
- Dnchc1, HL-3, p22, DHC1, CMT2O
- Chromosome:
- 14q32.31
- Locus Type:
- gene with protein product
- Date approved:
- 1995-11-15
- Date modifiied:
- 2016-03-02
Related products to: DNCH1 antibody
Related articles to: DNCH1 antibody
- We report the generation of a human induced pluripotent stem cell (hiPSC) line from peripheral blood mononuclear cells of a 14-year-old male with Autism Spectrum Disorder carrying a de novo heterozygous likely-pathogenic variation c.4067C>T (p.Pro1356Leu) in Dynein Cytoplasmic 1 Heavy Chain 1 (DYNC1H1) gene. Variation in this gene that encodes a motor protein may affect retrograde transport of neurotrophic signals, synaptic vesicles, organelles like golgi complex and mitochondria. Therefore, this iPSC line will be an invaluable tool to study the effects of this high-risk autism-related variant on disease manifestation and cellular functions. - Source: PubMed
Publication date: 2026/04/21
Niranjana Murthy Ashitha SiddappaChoudhary PrincySachdeva PranshuShankarappa BhagyalakshmiPaul PradipSud ReetekaManohar HarshiniUdupi Gautam ArunachalPurushottam MeeraJain SanjeevZafar ImtiazViswanath Biju - - Source: PubMed
Publication date: 2026/04/27
Vega GiadaCamussi DilettaAstrea GujaBartolini Emanuele - Although mutations in many genes cause familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), most cases are sporadic (sALS and sFTD) with unclear etiology. Here we tested whether somatic mutations contribute to sALS and sFTD by deep targeted sequencing of 88 neurodegeneration-related genes in postmortem brain and spinal cord samples from 399 sporadic cases and 144 controls. Predicted deleterious somatic variants in ALS/FTD genes were observed in 2.1% of sporadic cases lacking deleterious germline variants. These variants occurred at very low allele fractions (typically <2%) and were often focal and enriched in disease-affected regions. Analysis of bulk RNA-sequencing data from an additional cohort identified deleterious somatic variants in DYNC1H1 and LMNA, genes associated with pediatric motor neuron degeneration. Targeted long-read sequencing further identified one sFTD case with de novo somatic C9orf72 repeat expansions. Together, these findings suggest that rare, focal somatic variants can contribute to sALS and sFTD and drive widespread neurodegeneration. - Source: PubMed
Publication date: 2026/04/15
Zhou ZinanKim JunhoHuang August YueNolan MatthewPark JunseokDoan RyanShin TaehwanMiller Michael BBae MingyunZhao BoxunKim JinhyeongChhouk BrianMorillo KatherineYeh Rebecca CKenny ConnorNeil Jennifer ELee Chao-ZongOhkubo TakuyaRavits JohnAnsorge OlafOstrow Lyle WLagier-Tourenne ClotildeLee Eunjung AliceWalsh Christopher A - Impaired cytoplasmic dynein function has been implicated in amyotrophic lateral sclerosis (ALS) pathogenesis, yet the contributions of spinal interneurons to disease phenotypes remain unclear. We tested the hypothesis that hypomorphic dynein function in cholinergic neurons disrupts the development, survival, or positioning of inhibitory interneuron populations in the lumbar spinal cord. Using ChAT-Cre recombination, we generated four mouse genotypes with graded reductions in dynein activity in ChAT+ cells: Dync1h1+/+ (wildtype), Dync1h1-/+ (hemizygous wildtype), Dync1h1+/Loa (heterozygous Loa mutation), and Dync1h1-/Loa (hemizygous Loa). At 52 weeks of age, lumbar spinal cords (L3-L6) were harvested, cryosectioned, and immunostained for ChAT, GAD-67, Parvalbumin, and Calbindin. Cell counts were performed on confocal images from eight sections per mouse (N = 3 male mice/genotype), and radial distances from the central canal were normalised to gray matter width. Angular distributions were analysed via circular statistics. There were no significant genotype-dependent differences in the numbers of ChAT+, GAD-67+, Parvalbumin+, or Calbindin+ cells, nor in ChAT+ subpopulations (motor neurons versus interneurons) or double-positive interneuron subsets (e.g., ChAT+-GAD-67+, Parvalbumin+-GAD-67+, Parvalbumin+-Calbindin+). Radial positioning relative to the central canal was similarly preserved across all markers and genotypes. Circular-median tests revealed statistically significant shifts in mean angle for ChAT+, GAD-67+, and certain double-positive cells, but these amounted to only 5-10° displacements, translating to lateral shifts of ~10-20 µm, well within single laminar bands, and are unlikely to impact circuit connectivity. Despite substantial motor deficits and hallmark TDP-43 pathology previously seen in these models, impaired dynein function does not precipitate interneuron loss or gross migratory defects in the lumbar spinal cord. Instead, our findings suggest that the primary contributions of dynein to ALS-like phenotypes likely arise from functional disruptions in axonal transport, synaptic maintenance, and neuronal physiology rather than from structural alterations or loss of interneuron populations. - Source: PubMed
Publication date: 2026/04/02
Christoforidou EleniRowe Jordan SSimoes Fabio ACassel RaphaelleDupuis LucLeigh Peter NigelHafezparast Majid - : Factors modulating phenotypic variability in Rett syndrome (RTT, OMIM 312750) include X chromosome inactivation (XCI), type of variant, and/or disease modifiers. Emerging evidence also points to multi-locus genetic variants. Understanding the phenotypic variability associated with multi-locus genetic diagnoses in individuals with RTT and -related disorders would be important not only for accurate diagnosis, risk stratification and clinical management but also to explain symptoms that might not be typically associated with RTT. : We present a case series of five individuals with a diagnosis of RTT or an -related disorder with co-occurring genetic findings, including pathogenic variants, variants of unknown significance and chromosome duplications. Clinical features such as neurodevelopmental history and comorbid medical conditions were assessed alongside the genetic findings. : A review of 200 cases with RTT identified five cases (all females aged 7-27 years) with a co-occurring genetic finding. Each case harboured at least one additional genetic variant that included a beta thalassaemia trait, () missense variant, maternally inherited 22q12.3 to q13.1 duplication, 7p14.3 and () variants of uncertain significance and a pathogenic () variant. A rare triple genetic finding was illustrated in a single case, combining , , and variants. This case series supports the premise that RTT and -related disorders exist in a more complex neurogenetic spectrum than previously defined. It also emphasises the complexity within -related disorders. They are not static, and in the context of severe treatment resistant epilepsy, disorders can evolve over time, necessitating diagnostic reclassification. Although the co-occurrence of multiple genetic disorders in RTT and -related disorders is rare, these cases underscore the importance of considering cumulative genetic burden when evaluating individuals with atypical features or evolving neurodevelopmental phenotypes. - Source: PubMed
Publication date: 2026/02/27
Singh JatinderChishti SamiyaSantosh Paramala